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Stevens-Johnson syndrome: Pathogenesis, diagnosis, and management

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DOI: 10.1080/07853890701753664 · Source: PubMed


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Stevens-Johnson syndrome: Pathogenesis, diagnosis,
and management
Ribhi Hazin a; Omar A. Ibrahimi b; Moustafa I. Hazin c; Arash Kimyai-Asadi d
Harvard University, Faculty of Arts and Sciences, Cambridge, MA, USA
Harvard Medical School, Department of Dermatology, Massachusetts General
Hospital, Boston, MA, USA
Department of Internal Medicine, St. Joseph's Hospital & Medical Center, Phoenix,
DermSurgery Associates, Houston, Texas, USA

First Published on: 29 November 2007

To cite this Article: Hazin, Ribhi, Ibrahimi, Omar A., Hazin, Moustafa I. and
Kimyai-Asadi, Arash (2007) 'Stevens-Johnson syndrome: Pathogenesis, diagnosis,
and management', Annals of Medicine, 40:2, 129 - 138
To link to this article: DOI: 10.1080/07853890701753664


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Annals of Medicine. 2008; 40: 129–138
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Stevens-Johnson syndrome: Pathogenesis, diagnosis, and management


Harvard University, Faculty of Arts and Sciences, Cambridge, MA, USA, 2Harvard Medical School, Department of
Dermatology, Massachusetts General Hospital, Boston, MA, USA, 3Department of Internal Medicine, St. Joseph’s Hospital
& Medical Center, Phoenix, AZ, USA, and 4DermSurgery Associates, Houston, Texas, USA

Cutaneous drug reactions are the most common type of adverse drug reaction. These reactions, ranging from simple pruritic
eruptions to potentially life-threatening events, are a significant cause of iatrogenic morbidity and mortality. Stevens-
Johnson syndrome (SJS) is a serious and potentially life-threatening cutaneous drug reaction. Although progress has been
made in the management of SJS through early detection, prompt hospitalization, and immediate cessation of offending
agents, the prevalence of permanent disabilities associated with SJS remains unchanged. Nevertheless, despite being a
problem that is global in scope, government and health care agencies worldwide have yet to find a consensus on either
diagnostic criteria or therapy for this disorder. Here, we provide the internist and emergency room physician with a brief
review the SJS literature and summarize the latest recommended interventions with the hope of improving early recognition
of this disease and prevention of permanent sequelae and mortality that frequently complicate SJS.

Key words: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, intravenous immunoglobulins,
adverse drug reaction, drug hypersensitivity, dermatological emergencies, mucocutaneous lesions, HLA B1501/HLA B1502,
keratinocyte apoptosis

Introduction During this period, patients may complain of fever,

sore throat, chills, headaches, and malaise (7).
Stevens-Johnson Syndrome (SJS) is a life-threaten-
Persistent fever lasting longer than 4 weeks should
ing inflammatory mucocutaneous drug reaction (1–
raise suspicion of a concomitant infection, but
3). SJS, also known as erythema multiforme major,
studies have demonstrated that continued fever
lies on a continuum between erythema multiforme
may occur in up to 85% of cases even in the absence
minor, characterized by targetoid cutaneous lesions
of an associated infection (8). This is followed by the
encompassing less than 10% of the body surface
rapid onset of mucocutaneous lesions. Painful
area, and toxic epidermal necrolysis, characterized
erosions of the mucous membranes are common
by widespread mucocutaneous involvement affect-
and may affect any combination of the lip, oral
ing 30%–100% of the skin surface (Table I) (4). The
cavity, conjunctiva, nasal cavity, urethra, vagina,
initial diagnosis of SJS is based on clinical presenta-
gastrointestinal tract, and respiratory tract during
tion, but skin biopsies and direct immunofluores-
the course of the illness (9–11). Involvement of
cence studies of the skin are essential to rule out
mucous membranes is evident in approximately 90%
other conditions such as autoimmune bullous dis-
of affected patients, and the absence of mucous
ease (5,6).
membrane involvement should cast doubt on the
diagnosis of SJS. Mucous membrane involvement
can result in both short-term dysfunction and
Clinical manifestations
morbidity, as well as long-term complications due
SJS characteristically begins with vague upper to fibrosis and strictures. The characteristic skin
respiratory tract symptoms lasting up to 2 weeks. lesions seen in SJS are diffuse erythematous macules

Correspondence: Arash Kimyai-Asadi MD, DermSurgery Associates, 7515 Main, Suite 210, Houston, Texas 77030, USA. Fax: +1-713 791-9927. E-mail:
ISSN 0785-3890 print/ISSN 1365-2060 online # 2008 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS)
DOI: 10.1080/07853890701753664
130 R. Hazin et al.
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Table I. Classification of Stevens-Johnson syndrome and toxic

epidermal necrolysis (48,49). Key messages
Body surface area N Early recognition and immediate withdrawal
Classification involved of offending agents are critical to minimizing
Stevens-Johnson syndrome v10%
debilitating or potentially life-threatening
Overlap Stevens-Johnson syndrome/Toxic 10%–29% consequences of Stevens-Johnson syndrome
epidermal necrolysis (SJS).
Toxic epidermal necrolysis w30% N Pharmaceutical treatment of SJS remains
controversial, although intravenous immuno-
with purpuric, necrotic centers and overlying blister- globulins (IVIg) are thought to hold promise
ing (Figure 1). These cutaneous lesions often for the management of SJS.
become confluent in some areas, and often demon-
N A multidisciplinary approach, including
prompt transfer to a burns unit in severe
strate a positive Nikolsky sign, which is further
cases, is key to reducing the morbidity and
detachment of the epidermis with slight lateral
mortality associated with SJS.
pressure. Targetoid lesions are typically present
and are caused by epidermal necrosis in the center
of lesions (4,12). As involvement progresses, ulceration followed by scarring and stricture, result-
affected portions of the skin slough, resulting in ing in significant deterioration of function of the
widespread superficial ulcers and loss of the epider- affected organ systems. The organ most commonly
mal barrier (13). affected in this manner is the eye, where corneal
The characteristic mucocutaneous lesions involvement affects the majority of patients and may
(Figure 1) tend to develop suddenly during the result in corneal ulceration, perforation, and perma-
prodrome, and new lesions may continue to erupt for nent sclerotic changes (17–19). Indeed, the majority
up to 4 weeks. Thereafter, the lesions reepithelialize. of patients with SJS have long-term ocular compli-
The mucocutaneous lesions seen in the prodromal cations. Less common and generally less debilitating
period are often the predominant feature and may exist ocular complications of SJS include anterior uveitis,
in the absence of skin lesions. Arriving at an accurate iritis, keratitis, and conjunctivitis (17). Early con-
diagnosis can be challenging in cases that lack notice- sultation with and continued care by an ophthalmol-
able skin lesions (14). Thus, cultures of oral mucosa ogist is critical in all patients with significant ocular
are indicated to help differentiate SJS from other involvement or injury (17–19). Urethral erosions are
causes of sore lesions in the oral mucosa including another common complication of SJS and may result
stomatitis, or virus-induced sloughing (15,16). in genitourinary strictures (15,20–22). In the acute
For most patients, the most clinically significant setting, placement of a Foley catheter to maintain a
elements of SJS are the sequelae of mucosal patent urinary tract should be considered.

Figure 1. SJS in a patient on carbamazepine: Skin lesions demonstrating characteristic diffuse erythematous macules seen in SJS. The
macules are typically targetoid with necrotic centers, and overlying flaccid blisters.
A review of Stevens-Johnson syndrome 131
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Consultation with a urologist for evaluation and SJS but in the presence of allopurinol, further
management of urethral ulceration and strictures is strengthening the genetic association of the disorder
therefore warranted in patients with SJS (19–23). (46). The increased frequency of HLA-B*1501 and
Gastrointestinal involvement has also been HLA-B*1502 alleles amongst certain Asian popula-
described, primarily affecting the esophagus, and tions has prompted health care officials in endemic
often results in the development of esophageal regions to begin developing inexpensive tests to
webbing or stricture (24–26). In rare cases SJS identify at-risk individuals prior to prescribing them
may cause ulceration of the mucosa of other allopurinol or carbamazepine (44). Furthermore, the
gastrointestinal organs such as the colon (27). presence of the HLA-DQB1*0601 allele places
Respiratory involvement in SJS has been reported individuals at greater risk for the development of
in rare cases and is associated with poor prognosis SJS with ocular complications and strengthens the
(28,29). Pulmonary restriction may develop second- notion of an underlying immunogenetic susceptibil-
ary to SJS-induced scarring of the pulmonary tract ity to the development of SJS (46,47). These
(30,31). findings may aid clinicians in assigning appropriate
therapy and yield improved benefit-to-harm ratios in
patients with SJS.
SJS occurs at a rate of approximately 1–7 cases per
million people per year (32–34). The risk of Stevens-
Johnson syndrome remains low with any of its Considering an appropriate differential diagnosis in
associated causes (32). SJS is fatal in approximately patients with mucocutaneous erosions can help
5%–15% of cases (35). Both the incidence of the eliminate misdiagnoses associated with these condi-
condition and the associated mortality rate appear to tions (5,48). Among the most common disorders
be elevated in immunocompromised patients with mistaken for SJS are staphylococcal scalded skin
these risks correlating with worsening immune func- syndrome, toxic shock syndrome, exfoliative derma-
tion (36,37). Chronic viral infections, such as Epstein titis, erythema multiforme, autoimmune bullous
Barr virus and Human Immunodeficiency Virus diseases, and chemical burns. Toxic shock syndrome
(HIV), may also increase the risk of SJS indepen- and scalded skin syndrome, which are bacterial in
dently of the degree of immunosuppression (38–40). nature, result in similar-appearing epidermolysis but
Autoimmune disorders, such as systemic lupus are readily distinguishable from SJS following biopsy
erythematosus, have also been reported to predispose and immunofluorescence studies. Similarly, auto-
to the development of SJS (1,41,42). immune bullous disease can be distinguished from
A certain genetic predisposition may also confer SJS by the presence of IgA deposition in the former
increased risk of developing SJS on patients. In one conditions (48). The absence of IgA deposition is
study, the human leukocyte antigen (HLA) B1502 characteristic of skin specimens of SJS patients
allele was found in 100% of SJS patients, placing (48,49). Graft-versus-host disease (GVHD) is
individuals with that particular HLA allele at a 900 another established cause of SJS independently of
times greater risk of developing SJS than the general drug administration (50,51). Like SJS, graft-versus-
population (1). Given this genetic predisposition, host disease is mediated by cytotoxic T cells that
certain ethnic groups in Asia have been identified as result in epidermal necrosis and keratinolysis (52–
having an increased risk for SJS in comparison to the 54). Furthermore, the clinical and histological
general population (43). This genetic susceptibility appearance of GVHD can mimic SJS making
seems to have a strong association with specific distinguishing the two disorders challenging (54).
drugs such as carbamazepine (44). Although HLA- For instance, the blister fluid of both conditions
B*1502 confers greater risk of SJS on patients, this demonstrate the presence of CD8+ T cells, further
susceptibility is phenotype-specific. For instance, complicating the ability of clinicians to distinguish
Caucasian patients with the HLA-B*1502 allele do the two (55). Histologically, both GVHD and SJS
not demonstrate the same susceptibility to SJS as result in apoptosis of epidermal Langerhans cells
Asian patients with the same genotype (44,45). (LCs) and often show decreased numbers of such
Caucasian patients with the HLA-B*1502 genotype cells in the dermis (56). Because of the difficulty in
tolerate carbamazepine relatively well while 100% distinguishing the two disorders clinically and
of the Han Chinese patients with the genotype histologically, conducting a thorough history and
developed SJS following carbamazepine administra- physical examination as well as early dermatologic
tion (44,45). The presence of the HLA-B*1501 consultation remain the cornerstone of diagnosis in
allele also confers an increased risk of developing instances where both SJS and GVHD are part of the
132 R. Hazin et al.
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differential diagnosis (6,54). Incidentally, Lyme allopurinol, and terbinafine. There also appears to
disease also presents with targetoid lesions. be an increased risk of developing SJS with higher
However, unlike SJS, which is associated with dosages of offending medications (62,63).
numerous targetoid lesions, Lyme disease typically Although they have been implicated in rare cases,
presents with a single or small number of targetoid overall, vaccine administration and chemical expo-
lesions that surround a central dusky area represent- sure are rarely associated with SJS (64–66).
ing a tick bite site (57,58). Furthermore, mucosal Cyclooxygenase-2 inhibitors have also been impli-
involvement is not present in Lyme disease, and cated as potential underlying sources of the disorder
patients with SJS are generally ill and have a very (67). Recreational drugs such as cocaine (68) as well
rapid onset of lesions as compared to patients with as over-the-counter and alternative medicines have
erythema chronicum migrans. also recently been implicated as causes of SJS (69).
The diagnosis of SJS is generally made on clinical According to recent studies, as many as 64% of
grounds based on the presence of classic mucocu- individuals diagnosed with SJS have been exposed to
taneous lesions. In most cases confirmation of drugs suggesting that in up to one-third of cases no
the diagnosis should be sought by skin biopsies, specific etiology has been identified (70). Although
which typically reveal vacuolization of basal layer medications are the most common causative agents
keratinocytes associated with lymphocytes along the in adults, similar trends do not apply in the pediatric
dermal-epidermal junction and necrotic spinous population (5). In fact, SJS in pediatric patients is
layer keratinocytes (49,59–61). The typical histo- more commonly triggered by infectious organisms
pathological appearance of SJS is characterized by than adverse drug reaction (5). An awareness of this
apoptosis and necrosis of keratinocytes along with distinction is critical to arriving at an accurate
dermoepidermal detachment and lymphocytic infil- diagnosis and treatment of the condition.
tration of perivascular regions (4,6). Intraepidermal Underlying infections are the second most com-
vesicles and papillary dermal edema may be noted mon cause of SJS. The most commonly associated
in more papular lesions. In severe cases, subepider- infectious agents are listed in Table II. The most
mal blistering associated with full-thickness epider- common implicated organism is Mycoplasma pneu-
mal necrosis may be present, but this is generally moniae which is oftentimes seen in children and may
considered the hallmark of toxic epidermal necro- be the reason for widespread cases of SJS during
lysis. To distinguish this condition from autoim- Mycoplasma epidemics (71,72). Although other
mune blistering disorders, biopsies should be infectious etiologies have been identified as causative
submitted both for routine histopathology as well agents for the condition, most remain uncommon
as for direct immunofluorescence studies. with the exception of herpes simplex virus which has
been implicated in acute as well as recurrent bouts of
SJS in adults and children (71,73,74). Moreover, a
number of underlying malignancies, such as squa-
Etiology mous cell carcinoma of the lung, Hodgkin’s lym-
Although a variety of etiologies, such as infections phoma, and certain forms of leukemia have been
and underlying malignancies, have been implicated associated with SJS (75–77).
as potential causes of SJS, drugs remain the
predominant inciting agent (Table II). The most
commonly implicated drugs are sulfa derivatives,
nonsteroidal anti-inflammatory agents, penicillin- The exact pathophysiologic mechanism of SJS
related and cephalosporin antibiotics, antiepileptics, remains unknown. Various theories have implicated

Table II. Etiologies of Stevens-Johnson syndrome.

Etiologic agent Most frequently described

Viral AIDS, herpes simplex virus, Epstein-Barr, influenza, coxsackie, lymphogranuloma venereum, and variola
Bacterial Mycoplasma pneumoniae, typhoid, tularemia, diphtheria, and group A streptococci
Fungal Dermatophytosis, histoplasmosis, and coccidiomycosis
Protozoal Trichomoniasis, plasmodium
Drugs Sulfas, nonsteroidal anti-inflammatory drugs (NSAIDs), antiepileptics, barbiturates, allopurinol,
tetracyclines, antiparasiticsa
Sulfa drugs (96,107,120), antiepileptics (97,102,123,124,130), allopurinol (103,130), tetracyclines (104) are more common in the setting
of a compromised immune system (19,20,25,134), antiparasitic and antibacterial drugs (23,104,105), antiviral agents (48,119,120),
antifungal agents (24), NSAIDS (31,46,121,122), infectious etiologies (4,108,109,117,118).
A review of Stevens-Johnson syndrome 133
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both immunological and nonimmunological mecha- Table III. SCORTEN scale (91,92). One point is added for each
nisms, with the prevailing evidence suggesting positive variable. A patient’s mortality can be predicted by the
primary involvement of the immunologic response total number of points according to the following breakdown: 0–1
points53.2% mortality; 2 points512.1% mortality; 3
(78), in particular those mediated by memory
points535.3% mortality; 4–5 points58.3% mortality; w5
cytotoxic T cells (79). Although it was originally points590% mortality.
classified as a type IV, delayed hypersensitivity
reaction, it now appears that the immunological Variable Value
mechanisms governing the SJS reaction are initiated Age w40 year
by the Fas antigen, a cell surface molecule that can Malignancy Present
mediate apoptosis (80,81). Activation of the Fas Heart rate w120 per minute
signaling cascade leads to widespread keratinocyte Body surface area involved at day 1 w10%
Serum blood urea nitrogen (BUN) w10 mg/dL
apoptosis and subsequent epithelial necrosis. Early
Serum bicarbonate v20 mg/dL
treatment of SJS via intravenous immunoglobulins Serum glucose w14 mg/dL
(IVIg) blocks the activation of the Fas pathway, thus
underscoring the potential effectiveness of IVIg in
treating the disorder (35,82,83). Recent studies have are the most common cause of SJS, a thorough drug
also linked perforin, a pore-making monomeric history must be obtained, and all potential offending
granule released from natural killer T-lymphocytes agents must be immediately discontinued (32,39).
in the development of SJS. Perforin is believed to Indeed, immediate cessation of involved medica-
initiate the keratinolysis seen early in the develop- tions appears to improve the prognosis (93).
ment of SJS (84). Some evidence also exists linking Comprehensive SJS treatment requires a skilled,
IgE-mediated mechanisms and mast cell activation collaborative, multidisciplinary approach that
contributing to SJS (85). addresses the highly complex, systemic response to
Genetic factors may play a role in the development the condition. A multispecialty team may also assist
of SJS. It has been postulated that patients with slow in subsequent postdischarge management including
intrinsic acetylation rates and those taking medica- psychosocial issues that may arise from SJS-induced
tions such as azoles, protease inhibitors, serotonin- disfigurations or scarring. The management of
specific reuptake inhibitors, and quinolones are at milder cases of SJS may occur in an inpatient ward
increased risk of developing SJS (1,86–88). Slow with the same fundamental therapeutic protocol
acetylation may indeed be a factor in the develop- used for burns: warming of the environment,
ment of a number of adverse cutaneous drug minimizing transepidermal water loss, treatment of
reactions (89), as the reduced rate of acetylation electrolyte imbalances, administration of high-cal-
causes the accumulation of reactive metabolites that orie nutrition and intravenous fluids to prevent
induce cell-mediated cytotoxic reactions directed dehydration, and prevention of sepsis (38,39,94–
against the epidermis, resulting in keratinocyte 96). For patients with extensive cutaneous involve-
apoptosis (90). ment, prompt referral to a burns unit has been
shown to reduce the risk of infection, mortality, and
the length of hospitalization (94,96–101). This is
Treatment particularly true for SJS caused by drugs with short
SJS is a serious systemic disorder with the potential half-lives, which represent a positive prognostic
for severe morbidity and mortality. In approximately factor for SJS (94). Patients must be counseled
5%–15% of cases SJS is fatal (35,39). In order to regarding strict future avoidance of agents respon-
determine a patient’s risk of death with SJS, clinicians sible for the outbreak as well as chemically similar
are encouraged to use the SCORTEN (TEN-specific compounds. Given the suspected hereditary associa-
severity of illness score) scale which employs impor- tion with SJS, first-degree relatives should also be
tant prognostic indicators including heart rate, age, encouraged to avoid similar chemical compounds.
and renal function (91,92) (Table III). Assessing the Targeted nursing care including adequate main-
SCORTEN score requires giving the patient one tenance of topical management reduces associated
point for each positive variable his condition fulfills. morbidity and allows a more rapid reepithelialization
The total points are tallied, with increased scores of skin lesions and the prevention of scarring,
correlated with poorer prognosis. synechia formation, and infection (39,100). Skin
Effective management of SJS begins with prompt erosions should be covered with moisture-retentive
recognition of the entity, combined with attention to ointments and/or topical antibiotics to improve
each of the major organs that may be affected, as barrier function and to prevent bacterial infection.
well as potential comorbidities. Since medications Given the involvement of the lips and oral mucosa in
134 R. Hazin et al.
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many patients with SJS, adequate emphasis on analysis reported a 100% survival rate and com-
alleviating pain associated with lesions in the mouth plete skin healing in 12 patients with SJS after
is an integral part of treating the disorder. treatment with IVIg (115). However, the absence of
Application of petroleum jelly and sterile saline large or controlled trials raises questions regarding
compresses can promote rapid reepithelialization of the efficacy of IVIg, particularly given the high cost
the lips. The use of viscous lidocaine on the oral of this treatment (116). In the absence of clear-cut
mucosa in combination with diphenhydramine or benefits, potential risks of IVIg should be reviewed
sodium bicarbonate mouthwashes can dramatically with the patient prior to treatment.
relieve pain associated with friable mucocutaneous Sepsis is a major source of mortality in SJS
ulcerations and prevent the onset of odynophagia patients. However, prophylactic antibiotics are not
(102–104). recommended in the treatment of acute SJS except
For patients with ocular involvement, daily when the etiologic agent is identified as an infectious
erythromycin eye drops are recommended to prevent agent. For example, although supportive therapy
bacterial infections, and corticosteroid eye drops are was once considered treatment of choice for
administered to reduce inflammation (4). Continued Mycoplasma-induced SJS, antibiotic therapy is now
ophthalmologic care is recommended even after typically administered to treat the infection (72).
recovery in order to monitor and minimize irrever- The presence of an opportunistic infection due to
sible ocular complications including visual loss. HIV or immunosuppression represents a poor
Involvement of other organs is addressed with prognosis in the evolution of SJS and toxic epidermal
appropriate supportive care as well as treatment of necrolysis (TEN) (36,37,40).
any strictures, adhesions, or scarring that may Although prophylactic antibiotics are not recom-
complicate the course of the disease. Respiratory mended, the use of skin cultures on the first day and
involvement may require prompt intubation and every 48 hours thereafter is recommended as a
ventilatory support (28,29). means of monitoring possible bacterial growth.
The use of medications to treat SJS has met with Topical antibiotic treatment should begin if there
intense debate over the years. Treatment with is an increased number of bacteria cultured from the
corticosteroids, while effective in most other acute skin with selection of a single strain, a sudden drop
inflammatory disorders, is controversial (105–110). in temperature, and/or deterioration in the patient’s
Furthermore, numerous other anti-inflammatory, condition.
immunosuppressive, and immunomodulatory agents, Prompt and uninterrupted enteral nutrition
such as cyclosporin, cyclophosphamide, thalido- reduces the incidence of stress ulcers and bacterial
mide, and intravenous immunoglobulins (IVIg), translocation, and allows earlier discontinuation of
have been administered as possible means to arrest intravenous lines (39). Finally, treating the patient’s
underlying immunological mechanisms promoting existing health concerns is paramount. For example,
SJS (39,111,112). However, the efficacy of these regardless of whether SJS is suspected to be secondary
agents in the treatment of SJS has not been to a drug reaction, prophylactic use of anticoagulants
demonstrated by any controlled clinical trial. In maybe indicated due to the risk of thromboembolism-
the absence of strong evidence, none of these induced morbidity and mortality (1). Furthermore,
regimens can be definitively proposed as a treat- based on the severity of the disease, analgesics along
ment of choice. This notwithstanding, IVIg admi- with supportive emotional and psychological care
nistered early after the onset of mucocutaneous should be provided as needed.
lesions is thought to hold the most promise for
improvement in survival and a reduction in long-
term morbidity (82,83,113). The dose of IVIg
administered varies, but typically is 1–3 g/kg/day for SJS is a rare but serious adverse cutaneous reaction
3–5 days, with a mean total dose of 2.7 g/kg most commonly due to medications and infectious
divided over 1–5 days (23,70,114,115). Studies agents. Prompt recognition is critical for the initia-
have demonstrated that IVIg arrests Fas-mediated tion of appropriate care. The mainstay of treatment
keratinolysis in vitro, which provides a pathophy- remains addressing the causative agent as well as
siologic explanation of why it may improve SJS supportive care for the mucocutaneous ulcerations.
through disruption of Fas-induced keratinocyte This requires a multidisciplinary approach to all
apoptosis (83,109). Moreover, intravenous immu- organ systems that may be affected by this disease.
noglobulins have yielded promising results in In severe cases, prompt transfer to a burns unit is
controlled studies involving children (111) as well necessary in order to decrease both morbidity and
as adults (115). For example, a recent retrospective mortality. While systemic corticosteroids should be
A review of Stevens-Johnson syndrome 135
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